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Background: Human Herpes Virus 8 (HHV-8) is involved in autoimmunity. However, its association with advanced liver disease has not been fully explained. Herein, the prevalence of HHV-8 viremia was assessed in Iranian liver transplant candidates with a confirmed diagnosis of cirrhosis. Methods: This cross-sectional study was conducted on 230 patients with cryptogenic cirrhosis, virus-related cirrhosis, and autoimmune hepatitis, as well as 140 healthy blood donors from April 2022 to September 2023. The HHV-8 IgG antibody concentration and viral load were evaluated via ELISA and RT‒PCR, respectively. Results: Anti-HHV-8 IgG antibodies were detected in 25 cirrhotic patients (10.8 %) and four healthy individuals (2.6 %) (p = 0.022). The majority of the seropositive patients had cryptogenic cirrhosis (20.4 %), followed by autoimmune hepatitis (13.1 %) and virus-related cirrhosis (4.7 %). The seropositivity of HHV-8 IgG antibody was significantly different among the etiologies of liver cirrhosis (p = 0.011). However, HHV-8 genomic DNA was not detected in the sera of the patients or healthy blood donors. Conclusion: The role of HHV-8 infection in the development of posttransplant diseases, together with the higher seroprevalence of HHV-8 antibodies in cirrhotic patients than in healthy individuals, highlights the importance of both primary and latent infections in liver transplantation. Therefore, serological and molecular screening of HHV-8 is highly suggested for liver transplant candidates and organ donors. The possibility of antibody-mediated epitope mimicry in cryptogenic and autoimmune groups with moderate HHV-8 antibody positivity and negative viral loads may account for the development of advanced liver diseases.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease caused by genetic and environmental factors such as viral infections. Genomic and serologic tests were applied to detect significant blood-borne viruses in SLE patients to determine whether there was a possible association between viral infections and SLE. Methods: Antibodies (Abs) against HHV-8, HCMV, EBV, HIV, HBV, and HCV in SLE patients suffering from SLE were assessed by ELISA. In addition, HHV-8 DNA and HIV-1 RNA were quantified by real-time PCR, and the HCV and HBV genomes were detected using nested PCR. Results: Compared to those in the control group, a high prevalence of anti-HHV-8 (p

Abstract Background: Intrauterine endocrine abnormalities have profound effects on the development of physiological disorders. Objective: This study aimed to assess the effects of in utero exposure to letrozole (an aromatase inhibitor) and its late consequences on the reproductive and metabolic performance of an adult male offspring. Materials and Methods: 15 pregnant Sprague-Dawley rats (8 wk, 155 gr) were randomly assigned into 5 experimental groups (n = 3/each) and orally received either letrozole at doses of 0.25, 0.75, 1.00, and 1.25 mg/kg body weight (BW) or vehicle (control) on the gestation days of 16, 17, and 18. Pregnancy outcome, sexual behaviors on postnatal day 60, serum biochemical features, and the histopathology of testes were assessed in male offspring. Results: Compared to control group, delayed labor (21.83 vs. 24.25, p < 0.0001) and reduced litter size (n = 12.25 vs. n = 2, p < 0.0001) were recorded in 1.25 mg/kg BW group. A reduction in high-density lipoprotein level and the elevation of testes weight, BW gain, anogenital distance, as well as the serum concentrations of testosterone, triglycerides, cholesterol, and glucose were observed in 1.25 mg/kg BW (p < 0.0001) and 1.00 mg/kg BW (p < 0.0001) groups in comparison to control. A larger number of anogenital female sniffing, pursuit, and mounting behaviors were also observed in 1.25 mg/kg BW group in comparison to control (p < 0.0001). Severe testicular defects including necrosis and disruption of the epithelium of seminiferous tubules, sloughing of epithelial cells, and spermatogenesis arrest were observed in letrozole-treated groups, in a dose-dependent manner. Conclusion: Maternal exposure to letrozole can adversely affect the reproductive and metabolic performance of male offspring rats, suggesting an incomplete sex differentiation.

Background and purpose: P24 is one of the important components of retroviruses capsid. Several studies have shown the inhibitory effect of melittin protein on the function of AIDS virus. The aim of this study was to evaluate the effect of this protein on P24 in SIV and HIV viruses using bioinformatics software. Materials and methods: P24 protein sequences of SIV and HIV were obtained from a gene bank and their features were analyzed using different software programs. Also, structural similarities of P24 protein between SIV and HIV viruses were examined. Docking analysis was used to examine the interactions between melittin and P24 proteins. The stability of docking results were confirmed by molecular dynamics simulation. Results: Findings showed numerous phosphorylation, glycosylation sites, and di-sulfide bonds in P24 protein. Docking results indicated a probable interaction between P24 protein of both viruses and melittin. The results showed similarity of the third structure of P24 protein between the two viruses. Analysis of molecular dynamics showed molecular stability of the interactions between P24 and melittin proteins. Conclusion: High energy values of the interaction between melittin and P24 indicated high binding potential of the two proteins, which can determine the inhibitory effect of melittin on the function of HIV capsid. Analysis of the third structure of P24 protein in both viruses showed that they are very similar despite the high difference in protein sequences from the point of view of folding and 3D structure. Application of melittin to control SIV infections in primates can be used as a model for inhibiting HIV in humans.

The emergence of resistance to antiretroviral drugs is the main problem in their long-term efficacy and by considering the wide use of protease inhibitors (PIs), monitoring drug resistance mutations is necessary. Therefore, this study aimed to investigate the PIs drug resistance mutations in Iranian patients as well as subtyping using bioinformatics analysis. Fifteen Iranian patients living with Human Immunodeficiency Virus (HIV) (PLWH) were examined. RNA was used to amplify and sequence the HIV protease gene; also, HIV viral load was determined for all samples. The sequencing results were analyzed by several strong bioinformatics tools to determine the drug-resistance mutations and HIV subtypes. Some polymorphisms in the protease gene were recognized; however, there was no significant rate of major or minor drug resistance mutations in our studied patients. Subtyping analysis revealed the new subtype (D) and the previously reported ones, A and CRF-AD 35, in patients. This study confirmed that the resistance mutations and genetic polymorphisms of the protease region are rare in Iranian-infected patients that can be concluded that prescribing protease inhibitor class in HIV-infected patients is promising in controlling HIV in Iran. In addition, conducting periodic studies to determine the new mutations and the rate of drug resistance to PIs in Iranian individuals highlights the importance of WHO guidelines that recommends monitoring of genotypic-resistance testing and investigation of mutations in HIV-related genes.

Abstract Background NS5A and NS5B proteins of hepatitis C virus (HCV) are the main targets of compounds that directly inhibit HCV infections. However, the emergence of resistance-associated substitutions (RASs) may cause substantial reductions in susceptibility to inhibitors. Methods Viral load and genotyping were determined in eighty-seven naïve HCV-infected patients, and the amplified NS5A and NS5B regions were sequenced by Sanger sequencing. In addition, physicochemical properties, structural features, immune epitopes, and inhibitors-protein interactions of sequences were analyzed using several bioinformatics tools. Results Several amino acid residue changes were found in NS5A and NS5B proteins; however, we did not find any mutations related to resistance to the treatment in NS5B. Different phosphorylation and few glycosylation sites were assessed. Disulfide bonds were identified in both proteins that had a significant effect on the function and structure of HCV proteins. Applying reliable software to predict B-cell epitopes, 3 and 5 regions were found for NS5A and NS5B, respectively, representing a considerable potential to induce the humoral immune system. Docking analysis determined amino acids involved in the interaction of inhibitors and mentioned proteins may not decrease the drug efficiency. Conclusions Strong interactions between inhibitors, NS5A and NS5B proteins and the lack of efficient drug resistance mutations in the analyzed sequences may confirm the remarkable ability of NS5A and NS5B inhibitors to control HCV infection amongst Iranian patients. The results of bioinformatics analysis could unveil all features of both proteins, which can be beneficial for further investigations on HCV drug resistance and designing novel vaccines.

Mutations in tumor suppressor p53 protein can occur at different phases of malignant transformation and affect the patient's prognosis. This study aimed to evaluate the expression of mutant p53 protein in Iranian patients with the primary and recurrence oral squamous cell carcinoma (OSCC). This retrospective cross-sectional study conducted on a group of patients with the primary OSCC (n=122) and the control subjects with oral noncancerous reactive lesions (n=80). Immunohistochemistry was performed with the DO-7 monoclonal antibody against p53 protein, and samples with ≥10% immunostaining were considered positive. Statistical analyses were carried out using SPSS. Positive staining for p53 was observed in none of the control subjects and 57.4% (70 of 122) of the primary OSCC patients (p

Objective(s): Various therapeutic approaches, including stem-cell-based strategies and tissue engineering, have been proposed for oral ulcerative lesions. We investigated the effects of adipose tissue-derived stem cells (ADSCs) seeded onto the curcumin-loaded collagen scaffold in the mucosal healing of oral ulcers in rats.Materials and Methods: The current experimental study was conducted on 40 male Sprague-Dawley rats. Oral ulcers were created over both sides of buccal mucosa, and the rats were randomly divided into four equal groups: 1) an untreated group (negative control); 2) Teriadent-treated group (positive control); 3) group treated with curcumin-loaded collagen scaffold; and 4) group received the ADSCs (3 × 106 cells) seeded onto the curcumin-loaded collagen scaffold. Rats were sacrificed on 3rd and 7th day after ulceration for histopathological examination as well as measurement of tissue levels of myeloperoxidase (MPO), superoxide dismutase (SOD), and Interleukin-1 beta (IL-1β) activity. Results: Compared with the negative control, the tissue levels of MPO and IL-1β were significantly decreased in all treated groups (p

Objective(s): One of the essential problems in burn therapy is performing the permanent replacement of skin in full and deep thickness injuries. Human Wharton’s Jelly mesenchymal stem cells (HWJMSCs) have a unique combination of prenatal and postnatal properties. Decellularized human amniotic membrane (DHAM) can be used as a scaffold for HWJMSCs-therapy. We aimed to evaluate the quantity and quality of healing in the early excision burn wound dressing with 3-dimensional and 2- dimensional cell cultures.Materials and Methods: Amniotic and umbilical cords were isolated from the mothers who were candidates for cesarean section. HAM was decellularized using the mechanical and enzymatic method. HWJMSCs were isolated and cultured; cell surface markers were examined for authentication of MSCs and labeled using a viral vector containing the cGFP gene. Burns were created using brass bar in 32 adult male Albino rats and randomly divided into four groups (DHAM+HWJMSCs, injection of HWJMSCs, HWJMSCs was spread on the wound, and DHAM alone). Rats were sacrificed on the 7th and 14th days for pathological examination of the wound. Comparisons between the study groups were made by one-way analysis of variance.Results: Wound healing process in DHAM+HWJMSCs was much more progressed during the first week in comparison to other groups, and exhibited significant differences in re-epithelialization, formation of granulation tissue, and hemorrhage (PConclusion: The utility of the amniotic scaffold seeded by the human mesenchymal stem cells is recommended for accelerating the healing process.

Objective: Extensive research has been done to assess the efficacy of herbs for treating different disorders. Dorema ammoniacum (D. ammoniacum) is used in folk medicines for various goals. The application of herbs in medicine is accompanied by harmful effects. Chick embryo is considered a suitable model for assessing drugs toxicity. The present study aimed to evaluate the changes in vasculature in chick’s extra-embryonic membrane following D. ammoniacum treatment. Alterations in molecular pathways associated with early embryonic angiogenesis such as vascular endothelial growth factor A (VEGF-A) were also evaluated. Materials and Methods: Fertile chicken (Ross 308) eggs were allocated into three similar groups; sham, control and D. ammoniacum groups; in D. ammoniacum group, eggs were inoculated with plant’s extract at doses of 50 or 100 mg per kg egg-weight. Results: Analysis of the extra-embryonic membrane vasculature revealed that D. ammoniacum extract decreases some vascular parameters such as vessels area, total vessels length, vascular branch and increases lacunarity. This herb’s vascular toxicity was in a dose-dependent manner. Down-regulation of the expression of VEGF-A was also seen in the extract-treated extra-embryonic membrane. Conclusion: Vascular toxicity of D. ammoniacum was confirmed by data presented in this paper. We conclude that alteration of vascular parameters and gene expression might finally lead to embryo malformation due to D. ammoniacum consumption. Therefore, the use of this herb must be limited during the fetal growth period especially at doses higher than 50 mg per kg.

Background: Burn is a life-threatening problem which can lead to alteration in the expression of several genes. A folk medicine topical ointment made from Perovskia abrotanoides (P. abrotanoides) was extensively used in northern region of Iran for burn wound healing properties. Therefore, the current study aimed to examine the healing potency of P. abrotanoides ointment and the expression patterns of wound healing-related genes in rat experimental model of of burn.Methods: In an experimental study, scald burn was inflicted in 28 adult male Sprague-Dawley rats by pouring 2.5 cc of boiling water into a firm rubber ring (2 cm diameter) on the dorsal surface of skin for 10 seconds. Rats were randomly divided into four groups and treated for 7 consecutive days: P. abrotanoides ointmenttreated group; a vehicle-treated group, which received the complete ointment without P. abrotanoides part; silver sulfadiazine-treated group; and the control group which received no treatment. Animals were sacrificed and a full thickness skin biopsy was taken from the burn site. Finally, the relative quantification of gene expression was performed using the vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) as target genes and β2-microglobulin (β2M) as a reference gene.Results: VEGF was up-regulated during the first week of healing in P. abrotanoides ointment-treated group; however, the local expression of TGF-β was similar between the groups.Conclusion: P. abrotanoides ointment utilized in Iranian folk medicine can accelerate wound healing by producing VEGF.

Background: Calotropis procera Aiton (C. procera) is used in folk medicine to cure various diseases. However, the use of herbs in human medicine is sometimes associated with adverse effects. Chick embryo is a preclinical model relevant to assess adverse effects of drugs and herbs. Therefore, the current study aimed to assess the alteration of vascular branching patterns in the chick’s extra-embryonic membrane following C. procera treatment. Besides, the alteration in molecular cues involved in early embryonic vasculogenesis, such as vascular endothelial growth factor A (VEGF-A) was also quantified. Methods: In an experimental study, 30 fertile chicken eggs were divided into three equal treatment groups; sham control, and C. procera-treated groups whose cases were treated with C. procera extract at doses of 50 or 100 mg per kg of egg weight. Results: Quantification of extra-embryonic membrane vasculature showed that anti-vasculogenic effect of the herbal extract was revealed by a reduction in vessels area, total vessels length, vascular branch and increased lacunarity. The alterations were made in a dose-dependent manner. The relative expression levels of VEGF-A mRNA was also decreased in the herbal-exposed extra-embryonic membrane. Conclusion: Concerns about the side effect of C. procera during pregnancy were confirmed by data presented in this study. We concluded that altered early vascular development and gene expression might eventually lead to developmental defects in embryo following C. procera consumption.Therefore, the use of this herb must be limited at the time of fetal growth especially at the dosage higher than 50 mg per kg.

Objective(s): Wounds are physical injuries that cause a disturbance in the normal skin anatomy and function. Also, it has a severe impact on the cost of health care. Wound healing in human and mammalian species is similar and contains a complex and dynamic process consisting of four phases for restoring skin cellular structures and tissue layers. Today, therapeutic approaches using herbal medicine have been considered. Although the benefits of herbal medicine are vast, some medicinal plants have been shown to have wound healing effects in different experimental studies. Therefore, the current review highlights information about the potency of herbal medicine in the experimental surgical skin wound healing.Materials and Methods: Electronic database such as PubMed, Google Scholar, Scopus, and Medscape were searched for Iranian medicinal plants with healing activity in experimental surgical skin wounds. In this area, some of the most important papers were included.Results: There are numerous Iranian medicinal plants with skin wound healing activity, but clinical application and manufacturing are very low in comparison to the research volume.Conclusion: In normal instances, the human/animal body usually can repair tissue damage precisely and completely; therefore, the utilization of herbs is limited to special conditions or in order to accelerate the healing process.

We aimed to investigate the association of pretreatment host and/or viral related factors with sustained virological response (SVR) rate in chronic hepatitis C (CHC) infected patients. This cohort study was performed on 200 IFN-naïve Iranian CHC patients who were treated with pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV). Pretreatment levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood sugar (FBS), HCV load and genotype were determined, and the pattern of changes was monitored throughout the course of treatment. The baseline FBS value in the non-responder group was significantly higher than that of the SVR group. The SVR group showed a rapid and continuous decline of ALT/AST activity from the beginning of the treatment, while the ALT level was fluctuating in non-responder and relapse groups. Persistent normalization of transaminases during combination antiviral therapy was significantly associated with SVR rate. Besides, age and FBS levels had the greatest impact on SVR. Minocycline seems to be a safe and effective adjuvant in the management of patients with schizophrenia.

Background & Objective: Hepatitis C Virus (HCV) is one of the important risk factors for liver cirrhosis and hepatocellular carcinoma. Some of the host genetic factors such as interleukin 28B (IL-28B) may influence the response to the antiviral therapy. IL28B is a member of the interferon (IFN) family which causes an antiviral response. Previous studies indicated that rs12979860 polymorphisms of the IL-28B gene can influence persistent antiviral response. Therefore, in this study, the frequency of genotypes of rs12979860 polymorphisms in two groups of healthy and HCV infected Iranian individuals were evaluated. Materials & Methods: In this cross sectional study, PCR-RFLP method was used to evaluate the frequency of genotypes of rs12979860 polymorphisms in 105 healthy individuals and 105 chronic HCV infected patients. Results: The frequency of rs12979860 genotypes in healthy individuals was CC: 50.5%, CT: 45.7%, and TT: 3.8%. In HCV infected patients it was CC: 22.9%, CT: 63.8%, and TT: 13.3%. The frequency of rs12979860 genotypes had significant difference between two groups however it is not associated with sex. Conclusion: A significant difference was observed between healthy individuals and HCV infected patients in the frequency of rs12979860 genotypes. The favorable CC genotypes and unfavorable TT genotypes was more detected in healthy individuals and HCV infected patients, respectively.

Abstract INTRODUCTION: Prevalence of influenza A virus (Flu-A), respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) was assessed in children with acute respiratory infections (ARIs). METHODS: Nasopharyngeal aspirates and throat swabs were subjected to real-time polymerase chain reaction (PCR) to detect RSV and Flu-A and to conventional PCR to detect hMPV. RESULTS: Of the 156 children assessed, 93 (59.6%) carried at least one virus, with 35.9% positive for RSV, 14.1% for hMPV, and 9.6% for Flu-A. The prevalence of co-infections was 2.6%. CONCLUSIONS: The high detection rate may reflect increased sensitivity of real-time PCR compared to traditional PCR and viral culture.